A Notch Signalling Pathway Inhibitor for Patients With Advanced Breast Cancer (0752-014)

NCT ID: NCT00106145

Last Updated: 2015-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30
• Study Completion Date: 2011-08-31

Brief Summary

An investigational study to determine the safety/tolerability, and efficacy of a notch signaling pathway inhibitor in patients with metastatic or locally advanced breast cancer and other advanced solid tumors.

Conditions

Advanced Breast Cancer; Other Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part I - Arm 1

Group Type: EXPERIMENTAL

Comparator: MK0752, Notch Inhibitor

Intervention Type: DRUG

Dose escalating beginning with rising dose levels of 300, 450, and 600 mg/day in a continuous dosing schedule.

Part II - Arm 1

Group Type: EXPERIMENTAL

Comparator: MK0752, Notch Inhibitor - 450 mg

Intervention Type: DRUG

Dose 450 mg capsules daily for 28 day cycles.

Part III - Arm 1

Group Type: EXPERIMENTAL

Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off

Intervention Type: DRUG

Dose escalating in a repeating intermittent dosing schedule of 3 days on and 4 days off at rising dose levels of 450, 600, 800, 1000, 1200, and 1400 mg/day.

Part IV - Arm 1

Group Type: EXPERIMENTAL

Comparator: MK0752, Notch Inhibitor - 1 day on, 6 off

Intervention Type: DRUG

Dose escalating in a repeating intermittent dosing schedule of 1 day on/6 days off at rising dose levels of 600, 900, 1200, 1500, 1800, 2400, 3200 mg/day once weekly and then increase at 33% increments.

Part V - Arm 1

Group Type: EXPERIMENTAL

Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mg

Intervention Type: DRUG

Dose 350 mg capsules daily intermittent 3 days on/4 days off dosing. THIS DOSING SCHEDULE IS NO LONGER UNDER INVESTIGATION

Interventions

Comparator: MK0752, Notch Inhibitor

Dose escalating beginning with rising dose levels of 300, 450, and 600 mg/day in a continuous dosing schedule.

Intervention Type: DRUG

Comparator: MK0752, Notch Inhibitor - 450 mg

Dose 450 mg capsules daily for 28 day cycles.

Intervention Type: DRUG

Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off

Dose escalating in a repeating intermittent dosing schedule of 3 days on and 4 days off at rising dose levels of 450, 600, 800, 1000, 1200, and 1400 mg/day.

Intervention Type: DRUG

Comparator: MK0752, Notch Inhibitor - 1 day on, 6 off

Dose escalating in a repeating intermittent dosing schedule of 1 day on/6 days off at rising dose levels of 600, 900, 1200, 1500, 1800, 2400, 3200 mg/day once weekly and then increase at 33% increments.

Intervention Type: DRUG

Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mg

Dose 350 mg capsules daily intermittent 3 days on/4 days off dosing. THIS DOSING SCHEDULE IS NO LONGER UNDER INVESTIGATION

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women or men greater than or equal to 18 years of age
• ECOG status less than or equal to 2 (a measurement to determine your ability to perform daily activities)
• In Parts I, III, and IV, patient must have a histologically confirmed, metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. There is no limit on the number of prior treatment regimens
• In Part II, only breast cancer patients are eligible
• In Part V, only patients with Numb negative breast cancer (i.e., tumor shows Numb immunoreactivity in less than 10% of the neoplastic cells assessed) are eligible
• Patient has recovered from and is at least 2 weeks from previous antineoplastic therapy, including chemotherapy, biological therapy (including Herceptin), hormonal therapy, radiotherapy, or surgery

Exclusion Criteria

• Patient has had an investigational treatment in the preceding 21 days
• Uncontrolled congestive heart failure or myocardial infarction (heart attack) within 3 months of study start
• History of hepatitis B or C or HIV
• Patient has the presence of clinically apparent central nervous system metastases or carcinomatous meningitis. Patients with CNS metastases who have completed a course of radiotherapy and are clinically stable in the judgment of the investigator are eligible
• Patients with "currently active" second malignancy, other than non-melanoma skin cancer, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for prior malignancy and are considered by their physician to be at <30% risk of relapse

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Krop I, Demuth T, Guthrie T, Wen PY, Mason WP, Chinnaiyan P, Butowski N, Groves MD, Kesari S, Freedman SJ, Blackman S, Watters J, Loboda A, Podtelezhnikov A, Lunceford J, Chen C, Giannotti M, Hing J, Beckman R, Lorusso P. Phase I pharmacologic and pharmacodynamic study of the gamma secretase (Notch) inhibitor MK-0752 in adult patients with advanced solid tumors. J Clin Oncol. 2012 Jul 1;30(19):2307-13. doi: 10.1200/JCO.2011.39.1540. Epub 2012 Apr 30.

Reference Type: RESULT

PMID: 22547604 (View on PubMed)

Other Identifiers

2005_008

Identifier Type: -

Identifier Source: secondary_id

0752-014

Identifier Type: -

Identifier Source: org_study_id